FFA turnover measurements combined with lipid oxidation rate and assessment of body composition were used to investigate possible mechanisms of regulation of in vivo FFA metabolism and the inter-relationships between the metabolisms of FFA, carbohydrate, and lipoproteins. Our previous studies had shown that FFA mobilization was less per gram of fat in obese subjects. We also showed that a significant component of fatty acid turnover was non-oxidative disposal. To further examine the mechanisms of control of free-fatty acids, we have conducted studies of free-fatty acid turnover under two metabolic perturbations. One was the infusion of propranolol and the other was comparing individuals on a high-saturated fat and a low-fat, high carbohydrate diet. Propranolol infusion decreased the turnover of free-fatty acid, and this effect was greater in more obese individuals. During propranolol infusion, lipid oxidation was also increased, resulting therefore in a greatly decreased proportion of non-oxidative fatty acid disposal. During transfer to a high saturated fat diet, fatty acid production rates also declined and lipid oxidation increased, thus resulting in a significantly lower proportion of non-oxidative fatty acid disposal. The data suggest that the sympathetic nervous system plays a role in regulating the output of fatty acids from adipose stores and that obese individuals may differ in their sensitivity to this regulation. Finally, the non-oxidative component of fatty acid metabolism was lower in situations where lipid oxidation was increased. This may reflect inhibition of triglyceride re- esterification in sites other than adipose tissue.